As dosage forms for oral solid formulations in the field of medicaments and foods, tablets, capsules, granules, powders and the like are known, and development of an orally disintegrating tablet that quickly disintegrates when it is placed in the mouth or put into water, as a dosage form that is taken more easily by the elderly, children and aphagia patients, is desired.
An orally disintegrating tablet is required to have the property of disintegrating quickly in the oral cavity, and to have a sufficient hardness that, like conventional tablets, it may tolerate physical impacts in production, transportation and use.
Furthermore, it is desirable in view of drug compliance that unpleasant taste and irritation are suppressed and favorable taste is provided when the tablet is placed in the mouth.
Various orally disintegrating tablets have been reported. For example, Patent Literature 1 describes an orally disintegrating tablet comprising: a) mitiglinide calcium hydrate, which is a drug having a bitter taste, b) a crystalline cellulose, and c) a granulated product comprising at least one kind selected from aminoalkyl methacrylate copolymer E and the like as a masking agent, d) a sugar or sugar alcohol, and e) at least one kind selected from corn starch and a partially-pregelatinized starch. This literature explains that the crystalline cellulose is incorporated in a granulated drug product and has the effect of enhancing the dissolution properties of the drug, and does not describe the effect of the kind of the crystalline cellulose on the oral disintegration properties and tablet hardness. Furthermore, this literature describes that, in the case where a sugar alcohol that is difficult to compression-mold directly with the drug-containing granulated product is used, it is desirable that the sugar alcohol be used after granulating it in advance, and further describes that, in the case where D-mannitol is used as the sugar alcohol, a partially-pregelatinized starch is preferable as a binder, and that a partially-pregelatinized starch comprising a cold water-soluble component of about 10 to 20% by weight is preferable so as to suppress generation of tabletting failure and to impart a suitable tablet hardness and the property of quick oral disintegration. However, in this literature, D-mannitol is always granulated with corn starch which is added in the granulating process.
Patent Literature 2 describes an orally disintegrating tablet comprising granulated drug granules obtainable by wet-granulation by adding an aqueous solution comprising a monosaccharide to a powder comprising a drug, and also describes that it is preferable to incorporate a crystalline cellulose and corn starch, which are hardly-soluble components, and specifically describes that the crystalline cellulose is preferably used since it has a property by which the friability of the tablet can be improved by incorporation of a small amount of the crystalline cellulose. This literature describes that it is essential that the drug-containing powder be wet-granulated with an aqueous solution comprising a water-soluble monosaccharide, and excellent forming properties and disintegration properties as an orally disintegrating tablet can be obtained by doing so.
Patent Literature 3 describes an orally disintegrating tablet comprising (1) an active ingredient, (2) mannitol, (3) a crystalline cellulose and (4) at least two specific components selected from the group consisting of low-substituted hydroxypropyl cellulose, corn starch and carmellose, wherein the incorporation amounts of the respective components are 0.01 to 50% by weight for (1), 20 to 86% by weight for (2), 10 to 30% by weight for (3), and the incorporation amounts of each of the respective specific components (4) is 1 to 20% by weight, and the total of the specific components as incorporated is 3 to 60% by weight, with respect to 100% by weight of the disintegrating tablet, and the incorporated crystalline cellulose (3), in the form of an aggregate, has a bulk density of 0.18 g/cm3 or less. This literature explains that the desired effect of the orally disintegrating tablet described in this literature is achieved by the combination of the crystalline cellulose having a specific bulk density (3) and the at least two kinds of specific components selected from the group consisting of the low-substituted hydroxypropyl cellulose, corn starch and carmellose (4), and the desired effect cannot be obtained if either of these is absent.